The Origins of Lactase Persistence in Europe

[Brännvin]

The earliest adult milk drinkers came from central Europe – a finding which overturns the notion than sun-starved Scandinavians got there first.

Unlike more than half of the world's people, most northern Europeans can digest milk, thanks to a gene that enables lactose digestion throughout adulthood. It was thought this gene first arose in Scandinavia, where lactose tolerance is most common, because it is a way of getting vitamin D in places with little sunshine, says Mark Thomas of University College London.

His team have now narrowed down the emergence of the gene to a tribe of cattle herders living around 7500 years ago between the Balkans and central Europe.

The distribution of the gene mutation across the continent runs parallel to the spread of Linearbandkeramik (Linear Band Pottery) people, a Neolithic farming culture that lived in central Europe 7500 years ago. "It is likely that Linearbandkeramik dairy farmers were the first to drink fresh milk, without first processing it into yoghurt or cheese," Thomas says.

Journal reference: PLoS Computational Biology, DOI: 10.1371/journal.pcbi.1000491

[Allenson]

One of the stranger things about the distribution of lactase persistence is that it is highest in those areas that, according to most models anyway, began a herding/pastoral lifestyle the latest.

The highest frequencies of tolerance are clearly across the northwestern fringe/North Sea regions, stretching from Ireland to Britain and across the North Sea to Denmark, Noway and Sweden.

This map shows tolerance:



Whereas this one shows intolerance:



It's a very puzzling story as the modern distribution of tolerance is inverse to the way in which pastoralism and milk drinking supposedly spread.

My feeling is that the jury is still very much out on the matter.

[Frigga]

Lactase is in raw milk. If you do not pasturize milk, the lactase in the milk will digest the lactose. Simple experiment on anyone's part: Get a glass of fresh raw milk. Take a taste, and then leave it on the counter all day. It will naturally sour. That is because of the lactase in the milk that digests the lactose, effectively preserving the milk naturally. Most people really do have problems with lactose, especially in the last one hundred years because of the mass cooking of our milk which kills the beneficial enzyme lactase. Simple solution for those who want to drink milk, drink it raw!

Real Milk

[Brännvin]

My feeling is that the jury is still very much out on the matter.

I agree with you a little bit too, here's an interesting quote from the NY Times from an article titled "The Genetic Map of Europe" based on an interview with Manfred Kayser, a geneticist at the Erasmus University Medical Center in the Netherlands;

"Genomic sites that carry the strongest signal of variation among populations may be those influenced by evolutionary change, Dr. Kayser said. Of the 100 strongest sites, 17 are found in the region of the genome that confers lactose tolerance, an adaptation that arose among a cattle herding culture in northern Europe some 5,000 years ago. Most people switch off the lactose digesting gene after weaning, but the cattle herders evidently gained a great survival advantage by keeping the gene switched on through adulthood."

http://www.nytimes.com/2008/08/13/sc...sual.html?_r=1

[Rochefaton]

There is something I have noticed through reading varies studies on LTP, and that is this; there may be a correlation between the distribution of Y-DNA R1b and the C-13.9kbT SNP, which is the SNP that is generally responsible for lactose tolerance in European populations.

First here are a few studies to show what I mean:

http://www.pnas.org/content/104/10/3736.abstract

"The T allele of C/T polymorphism located 13,910 bp upstream of the lactase (LCT) gene (−13.910*T) has been shown to associate strongly with LP in Europeans (3), and recent in vitro studies have indicated that it can directly effect LCT gene promoter activity (4)."

"Based on the decay of long-range haplotypes and variation in closely linked microsatellites, the inferred age of the −13.910*T allele in Europe has been estimated to be between 2,188 and 20,650 years (16) and between 7,450 and 12,300 years (17), respectively. These dates bracket archaeological estimates for the introduction of domestic cattle breeds into Europe (18), and when considered in conjunction with the modern frequency distribution of the −13.910*T allele in Europe, they indicate a strong selective advantage to LP."

"We obtained genotypes from eight Neolithic skeletons of central, northeast, and southeast Europe ranging in age between 5800 and 5000 B.C. (Table 1). One Mesolithic sample typed is absolutely younger [2267 ± 116 calibrated date (cal) B.C.] Additionally, we typed one Medieval skeleton as a control. We identified 9 of 10 individuals as homozygous C at position −13.910; all were Mesolithic and Neolithic samples. The one Medieval individual was heterozygous for the −13.910-C/T polymorphism. This was the only heterozygous individual, and it never showed allelic dropout."

Here is a list of the sampled skeletons and which culture, timeframe, mtDNA haplotype, etc. they belond to:

http://www.pnas.org/content/104/10/3...expansion.html

The above study shows that there was little if any LTP people in those parts of Europe 7,000 years ago.

Next is a study on LTP in Cameroon, which most people know is a hot spot for Y-DNA R1b1*:

http://dienekes.50webs.com/blog/archives/000553.html

"The ability to digest the milk sugar lactose as an adult (lactase persistence) is a variable genetic trait in human populations. The lactase-persistence phenotype is found at low frequencies in the majority of populations in sub-Saharan Africa that have been tested, but, in some populations, particularly pastoral groups, it is significantly more frequent. Recently, a CT polymorphism located 13.9 kb upstream of exon 1 of the lactase gene (LCT) was shown in a Finnish population to be closely associated with the lactase-persistence phenotype (Enattah et al. 2002). We typed this polymorphism in 1,671 individuals from 20 distinct cultural groups in seven African countries. It was possible to match seven of the groups tested with groups from the literature for whom phenotypic information is available. In five of these groups, the published frequencies of lactase persistence are 25%. We found the T allele to be so rare that it cannot explain the frequency of the lactase-persistence phenotype throughout Africa. By use of a statistical procedure to take phenotyping and sampling errors into account, the T-allele frequency was shown to be significantly different from that predicted in five of the African groups. Only the Fulbe and Hausa from Cameroon possessed the T allele at a level consistent with phenotypic observations (as well as an Irish sample used for comparison). We conclude that the C-13.9kbT polymorphism is not a predictor of lactase persistence in sub-Saharan Africans. We also present Y-chromosome data that are consistent with previously reported evidence for a back-migration event into Cameroon, and we comment on the implications for the introgression of the -13.9kb*T allele."

What is the only thing that Fulbe, Hausa, and Irish men have in common? A high frequency of R1b!

Next, is a map that shows the modern percentages of lactose intolerance for the given regional European populations:



The more lactose tolerant populations are those that contain more Y-DNA R1b individuals or the ones that are in close contact with R1b carriers. Even in the sampled Finnish populations, the more tolerant ones was the two with a higher frequency of R1b. (Correct me if I am wrong on that statement. I believe I remember reading that R1b is more prevelant in the west of Finland, but I can't find the source.)

Now you may be thinking to yourself, "But wait, Northern Europe is also very high in Y DNA I1. Maybe they spread the LTP gene around". That may be true, but that doesn't explain why a population that carries a more archaic form of R1b, such as the Cameroonians which carry no Y-DNA I, carry the −13.910*T allele.

Personally, I believe the −13.910*T allele could have been passed on to Northern European I1 populations via genetic drift from incoming R1b pastoralists. Once the SNP was introduced to Northern Europe it's frequency was amplified by natural selection, since Northern Europe is obviously a place where LTP would be advantagous due to low levels of sunlight and the lack of vitamin D.

Moving along now. Here is another map. This one shows a pattern of lactose intolerance becoming more prevalent as one heads southeast in Europe:



Now if you will compare the above map to the map below, you may seem similarities:



At this point, I believe that R1b made it's way to Europe with pastoralism and LTP, and once it reached Europe it came in contact with mtDNA H and that increased it's chances of survival. It seems a higher fertility rate is possessed by a man that has both Y-DNA R and mtDNA H as compared to a man that has a Y-DNA I and mtDNA H combo.

http://dienekes.blogspot.com/2008/05...abstracts.html

"The frequency of the combination mtDNA-haplogroup H (especially with the CRS sequence) and Y-haplogroup R was higher in fertile than in infertile men seemingly to be favorable to fertility. On the other hand, a considerable number of infertile men belonging to mtDNA-haplogroup H (CRS) and to Y-haplogroup I, associated to a specific DAZ gene deletion pattern- 2+4d, suggests a non favorable combination to male fertility."

The above could also explain R1b's absurd frequency levels in Western Europe.

Does anyone think this is plausible? This is just my own personal theory based on research done in my spare time, so it could be way off the mark, but I believe there may be some truth to at least parts of it.

Other explanations could be that R1b mutated in Western Europe and it took the −13.910-C/T polymorphism to Cameroon via Gibraltar, but that is in conflict with Cruciani's 2002 findings which point to a likely R1b1* entry from the Mid-East via Egypt.

Or, that the −13.910-C/T polymorphism was already present in an ancestoral R1* population and it became naturally selected by both R1b and R1a popualtions due to their pasotralist lifestyles.

[Tabiti]

Lactose tolerance is not directly linked with race, but way of live. Southern Europeans were mostly farmers, so they didn't drink that much milk to survive, unlike the Northern ones and those leading nomadic and semi-nomadic way of living.

[Allenson]

At this point, I believe that R1b made it's way to Europe with pastoralism and LTP, and once it reached Europe it came in contact with mtDNA H and that increased it's chances of survival. It seems a higher fertility rate is possessed by a man that has both Y-DNA R and mtDNA H as compared to a man that has a Y-DNA I and mtDNA H combo.

I'll have a look at the studies you posted, AlabamaMan. But in the meantime, I'll just chime in with this: goold ol' Polako on DNA-Forums has postulated some type of advatage inherent in R1b/H pairings as well.... So yes, perhaps there is something to this. I'm an R1b fellow who is still waiting on his mtDNA results!

[Frigga]

Personally, I don't buy into lactose tolerance being linked to genetics. There's too much ancedotal evidence to the contrary. Why else would milk drinking be so widespread throughout Africa, the Middle East, Asia along with Europe?

[Rochefaton]

Personally, I don't buy into lactose tolerance being linked to genetics. There's too much ancedotal evidence to the contrary. Why else would milk drinking be so widespread throughout Africa, the Middle East, Asia along with Europe?

There are different genes that allow lactase persistance in adults throughout the Old World, but that is widely known, and is not the issue here.

The point I am making is this: Y-DNA R1b and the C/T-13910 SNP, which is the lactase persistent SNP found amongst Europeans, are both found in Cameroonians and a few other African populations, but not in non-R1b carrying lactase persistent African populations. The other African groups possess different SNPs that allow them to digest milk.

Since the only link between Cameroonians and Europeans, other than the C/T-13910 SNP, is a strong presence of Y-DNA R1b, I am suggesting, as did one of the studies I posted, that it is very likely that an R1b carrying population spread the European type of lactase persistence SNP to Africa, and that an R1b population may also be responsible for that gene's presence in Europe.

[Tabiti]

And what about females?